Effect of intracarotid papaverine on human cerebral blood flow and vascular resistance during acute hemispheric arterial hypotension

This study assessed the feasibility of augmenting cerebral blood flow (CBF) and decreasing hemispheric cerebrovascular resistance (CVR) by intracarotid papaverine during acute cerebral hypotension. Awake patients (n = 10) undergoing transfemoral balloon occlusion of an internal carotid artery (ICA) with nitroprusside (SNP)-induced systemic hypotension (10% reduction of mean arterial pressure) were studied. We measured mean femoral artery pressure (MAP), mean distal ICA pressure (P(ica)), and CBF (intracarotid 133Xe) at two time points: before and after intracarotid papaverine infusion (1 or 7 mg/min). Two patients became symptomatic immediately after ICA occlusion and were excluded. One patient developed a focal seizure during papaverine infusion. In another, the occlusion balloon deflated prematurely. Of the remaining six patients, two of the three patients who received high-dose papaverine (7 mg/min) developed transient obtundation. The remaining three patients, who received low-dose papaverine (1 mg/min), did not develop any neurologic symptoms. There was a trend for intracarotid papaverine to increase hemispheric CBF by 36% (33 +/- 10 versus 45 +/- 22 ml x 100 g(-1) x min(-1), P = .084, n = 6); papaverine decreased CVR from 1.3 +/- 0.4 to 1.0 +/- 0.3 mm Hg x ml(-1) x 100 g(-1) x min(-1) (P = .049). There was no significant change in heart rate, MAP, or P(ica) during experimental protocol. Manipulation of CVR by intracarotid papaverine during acute hemispheric arterial hypotension appears to be feasible. Further studies are needed to establish safety and efficacy.     

Predictors and clinical implications of shivering during therapeutic normothermia

Background

Shivering during induced normothermia (IN) remains a therapeutic limitation. We investigated potential risk factors and clinical implications of shivering during IN.

Methods

Post hoc analysis was performed on 24 patients enrolled in a clinical trial of an automated surface cooling system to achieve IN. Hyponatremia was defined as serum levels <136 mmol/L and hypomagnesaemia as levels <1.5 mg/dL. Continuous heat energy transfer (kcal/h) was averaged hourly. Glasgow Coma Scale (GCS) scores were recorded every 2 h. Shivering status was documented hourly. Mixed effects modeling was used to determine clinical measures associated with shivering. Generalized estimating equation (GEE) models were used to compare baseline-adjusted repeated-measures GCS scores.

Results

About of 24 (39%) patients demonstrated shivering. Shivering was associated with men (67% vs. 21%, P = 0.03), hyponatremia (44% vs. 7%, P = 0.03), and hypomagnesaemia (56% vs. 7%, P = 0.02). The average kcal/h (158 ± 645 kcal/h vs. 493 ± 645 kcal/h, P = 0.03) was greater in shivering patients. Shivering was positively associated with increases in heart rate (P < 0.001), respiratory rate (P < 0.001), and kcal/h (P < 0.001). Non-shivering patients showed a greater increase from baseline GCS (GEE, P = 0.02) at 24 h. No differences in sedative doses or fever burden were noted between shiverers and non-shiverers.

Conclusions

Men, hyponatremia, and hypomagnesaemia may predispose febrile patients treated with IN to shivering. Shivering dramatically increases the amount of heat transfer required to maintain normothermia, and may be associated with adverse effects on level of consciousness.     

Intracarotid Nitroprusside Does Not Augment Cerebral Blood Flow in Human Subjects

Background: The recent resurgence of interest in the cerebrovascular effects of nitroprusside can be attributed to the possibility of using nitric oxide donors in treating cerebrovascular insufficiency. However, limited human data suggest that intracarotid nitroprusside does not directly affect cerebrovascular resistance. In previous studies, physiologic or pharmacologic reactivity of the preparation was not tested at the time of nitroprusside challenge. The authors hypothesized that if nitric oxide is a potent modulator of human cerebral blood flow (CBF), then intracarotid infusion of nitroprusside will augment CBF.

Methods: Cerebral blood flow was measured (intraarterial 133Xe technique) in sedated human subjects undergoing cerebral angiography during sequential infusions of (1) intracarotid saline, (2) intravenous phenylephrine to induce systemic hypertension, (3) intravenous phenylephrine with intracarotid nitroprusside (0.5 [mu]g [middle dot] kg-1 [middle dot] min-1), and (4) intracarotid verapamil (0.013 mg [middle dot] kg-1 [middle dot] min-1). Data (mean +/- SD) were analyzed by repeated-measures analysis of variance and post hoc Bonferroni-Dunn test.

Results: Intravenous phenylephrine increased systemic mean arterial pressure (from 83 +/- 12 to 98 +/- 6 mmHg; n = 8;P < 0.001), and concurrent infusion of intravenous phenylephrine and intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with intravenous phenylephrine or with concurrent infusions of intravenous phenylephrine and intracarotid nitroprusside. Intracarotid verapamil increased CBF (43 +/- 9 to 65 +/- 11 ml [middle dot] 100 g-1 [middle dot] min-1;P < 0.05).     

Pharmacodynamics and Pharmacokinetics of Cisatracurium in Geriatric Surgical Patients

Background: Cisatracurium, one of ten stereoisomers that comprise atracurium, is more potent than atracurium and has less propensity to release histamine. This study compares the pharmacokinetics and pharmacodynamics of cisatracurium in elderly and young patients.

Methods: Twelve elderly (aged 65-82 yr) and 12 younger patients (aged 30-49 yr) were anesthetized with nitrous oxide, fentanyl, and isoflurane (0.7%, end-tidal). The mechanomyographic response to train-of-four stimulation was assessed every 15 s after the administration of cisatracurium (0.1 mg/kg). Arterial samples were obtained over 6 h. Plasma cisatracurium concentration versus time data were fit to compartmental models. Pharmacokinetic parameters were determined assuming that elimination occurred from the central compartment only. This provides accurate clearance and half-life estimates but underestimates Vss (reported herein as Vss '). The pharmacodynamic response was described by the neuromuscular blocking profile.

Results: Onset to 90% paralysis (mean+/-SD) was delayed in the elderly (3.4+/-1.0 vs. 2.5+/-0.6 min). Recovery profiles were the same for both groups. Elimination half-life was minimally prolonged in the elderly (25.5+/-3.7 vs. 21.5 +/-2.4 min). The Vss ' was larger in the elderly (126 +/-16 vs. 108+/-13 ml/kg), although the clearances were the same for the two groups (5.0+/-0.9 vs. 4.6+/-0.8 ml *symbol* kg sup -1 *symbol* min sup -1).     

Trying versus liking fruits and vegetables: correspondence between mothers and preschoolers

Extensive research indicates that a diet rich in fruits and vegetables (F&V) protects against numerous illnesses in adulthood, but that most individuals, including children, consume far fewer F&V per day than is recommended. Since evidence suggests that eating habits in childhood track into adulthood, more research is necessary to learn about how parental F&V intake and opportunities influence child F&V consumption. The purpose of this study was to examine the relationship between mothers' F&V preferences and those of their preschool-age children to determine if greater maternal "liking" of fruits and vegetables was associated with their reports of their children's "trying" more fruits and vegetables. Eighty-three mothers completed a questionnaire that assessed whether they and their preschoolers had tried or liked a variety of F&V. Mothers liked 86% of the fruits they tried, girls 76%, and boys 69%. Mothers liked 81% of the vegetables they tried; boys and girls liked 55%. Mothers' likes correlated with F&V that their children tried, but mothers' likes also limited the number of F&V that their children tried. Mothers reported preferences for F&V are associated with estimates of their preschoolers' preferences for F&V. Relative to girls, boys may need additional opportunities for F&V exposure.